ArticleMolecular systems biology2013
Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.
Article in Molecular systems biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
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- Construction and validation of an EGFR-related risk signature identifiedTranslational cancer research · 2025Article
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- Novel HDAC11 inhibitors suppress lung adenocarcinoma stem cell self-renewal and overcome drug resistance by suppressing Sox2.Scientific reports · 2020Article
- A yeast display immunoprecipitation screen for targeted discovery of antibodies against membrane protein complexes.Protein engineering, design & selection : PEDS · 2019Article
- Functional RNAi Screens Define Distinct Protein Kinase Vulnerabilities in EGFR-Dependent HNSCC Cell Lines.Molecular pharmacology · 2019Article
- A Cross-Linking-Aided Immunoprecipitation/Mass Spectrometry Workflow Reveals Extensive Intracellular Trafficking in Time-Resolved, Signal-Dependent Epidermal Growth Factor Receptor Proteome.Journal of proteome research · 2019Article
- Functional Proteomics and Deep Network Interrogation Reveal a Complex Mechanism of Action of Midostaurin in Lung Cancer Cells.Molecular & cellular proteomics : MCP · 2018Article
- Correlation analysis of mesenchymal-epithelial transition factor protein and human epidermal growth receptor 2 protein expression in 1479 cases of lung adenocarcinoma in China.Thoracic cancer · 2018Article
- CAR-T cells and combination therapies: What's next in the immunotherapy revolution?Pharmacological research · 2018Article
- Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.PLoS biology · 2018Article
- Transcriptionally inducible Pleckstrin homology-like domain, family A, member 1, attenuates ErbB receptor activity by inhibiting receptor oligomerization.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
Abstract
We hypothesized that elucidating the interactome of epidermal growth factor receptor (EGFR) forms that are mutated in lung cancer, via global analysis of protein-protein interactions, phosphorylation, and systematically perturbing the ensuing network nodes, should offer a new, more systems-level perspective of the molecular etiology. Here, we describe an EGFR interactome of 263 proteins and offer a 14-protein core network critical to the viability of multiple EGFR-mutated lung cancer cells. Cells with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) had differential dependence of the core network proteins based on the underlying molecular mechanisms of resistance. Of the 14 proteins, 9 are shown to be specifically associated with survival of EGFR-mutated lung cancer cell lines. This included EGFR, GRB2, MK12, SHC1, ARAF, CD11B, ARHG5, GLU2B, and CD11A. With the use of a drug network associated with the core network proteins, we identified two compounds, midostaurin and lestaurtinib, that could overcome drug resistance through direct EGFR inhibition when combined with erlotinib. Our results, enabled by interactome mapping, suggest new targets and combination therapies that could circumvent EGFR TKI resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.